Membrane transport in eucaryotes will be studied by a comination of kinetic, genetic and biochemical analysis. Additional studies will be carried out on the membrane glycoprotein(s) implicated in transport function and altered in particular transport deficient mutants. This glycoprotein is unique in that an RNA moiety appears to be covalently attached to the core protein. The properties and function of such a molecule will be investigated in mutants of Neurospora crassa. A fine structure genetic anaysis will be carried out on the Pm N (neutral amino acid) transport locus. These studies will be combined with a kinetic analysis which suggests an allosteric modification of this system in Neurospora. Baseline studies will be extended for amino acid and polyamine transport in human fibroblasts. Amino acid and polyamine pool analysis will be carried out with various mutants of Neurospora and of man. Particular attention will be given to a class of mutants called "bradytrophs." Nutritionally they are near normal but do not produce sufficient end product to properly regulate and therefore tend to accumulate amino acids. They are often analog resistant and transport deficient. They appear to exist in man as well as microorganisms. BIBLIOGRAPHIC REFERENCES: Stephens, R.L. and DeBusk, A. Gib. B-galactosidases from neurospora crassa. Methods in Enzymology, Volume 42, Carbohydrate Metabolism, (1975). Rao, Edith Y., T. Karmeswar Rao and DeBusk, A. Gib. Isolation and Characterization of a Mutant of Neurospora crassa. Deficient in General Amino Acid Permease Activity. Biochim. Biophys. Acta. 413:45. (1975).